Introduction: Upregulated microtubule-associated serine/threonine kinase like (MASTL), a cell cycle kinase required for a progression through mitosis, expression has been associated to poor prognosis. This study aimed to investigate the clinical relevance of MASTL expression in oral squamous cell carcinoma (OSCC) and a possible mechanistic link with epithelial-mesenchymal transition (EMT). Methods: Immunohistochemical analysis of MASTL, E-cadherin, vimentin, and Smad7 was performed in paraffin-embedded tissue specimens from 148 OSCC patients. Results: Nuclear MASTL expression was detected in 115 (77.7%) OSCC specimens. High MASTL expression was significantly associated with the male gender, smoking habit, T stage, early clinical stage, and absence of vascular invasion. MASTL expression was inversely correlated with Smad7, whereas no association was observed with E-cadherin and vimentin. Patients harboring tumors with low MASTL expression exhibited a poorer overall survival. Smad7 expression was significantly related to reduced disease-specific and overall survival. High levels of MASTL expression were associated with better prognosis in T3 patients, N0 cases, and patients treated by surgery combined with radiotherapy and chemotherapy. Conclusion: The present study uncovers MASTL as a good prognostic factor in OSCC and a potential link with EMT via Smad7.

1.
Graillon
N
,
Iocca
O
,
Carey
RM
,
Benjamin
K
,
Cannady
SB
,
Hartner
L
, et al
.
What has the National Cancer Database taught us about oral cavity squamous cell carcinoma
.
Int J Oral Maxillofac Surg
.
2022
;
51
(
1
):
10
7
.
2.
Shah
J
,
Patel
S
,
Singh
B
Jatin shah’s head and neck surgery and oncology
. 4th ed.
Maryland Heights, MI, USA
:
Mosby
;
2019
; p.
245
95
.
3.
Sung
H
,
Ferlay
J
,
Siegel
RL
,
Laversanne
M
,
Soerjomataram
I
,
Jemal
A
, et al
.
Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
.
CA Cancer J Clin
.
2021
;
71
(
3
):
209
49
.
4.
Torralba
MG
,
Aleti
G
,
Li
W
,
Moncera
KJ
,
Lin
YH
,
Yu
Y
, et al
.
Oral microbial species and virulence factors associated with oral squamous cell carcinoma
.
Microb Ecol
.
2021
;
82
(
4
):
1030
46
.
5.
Mortazavi
H
,
Baharvand
M
,
Mehdipour
M
.
Oral potentially malignant disorders: an overview of more than 20 entities
.
J Dent Res Dent Clin Dent Prospects
.
2014
;
8
(
1
):
6
14
.
6.
Zanoni
DK
,
Montero
PH
,
Migliacci
JC
,
Shah
JP
,
Wong
RJ
,
Ganly
I
, et al
.
Survival outcomes after treatment of cancer of the oral cavity (1985-2015)
.
Oral Oncol
.
2019
;
90
:
115
21
.
7.
Hanahan
D
,
Weinberg
RA
.
The hallmarks of cancer
.
Cell
.
2000
;
100
(
1
):
57
70
.
8.
Marzec
K
,
Burgess
A
.
The oncogenic functions of MASTL kinase
.
Front Cell Dev Biol
.
2018
;
6
:
162
.
9.
Gharbi-Ayachi
A
,
Labbé
JC
,
Burgess
A
,
Vigneron
S
,
Strub
JM
,
Brioudes
E
, et al
.
The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A
.
Science
.
2010
;
330
(
6011
):
1673
7
.
10.
Mochida
S
,
Maslen
SL
,
Skehel
M
,
Hunt
T
.
Greatwall phosphorylates an inhibitor of protein phosphatase 2Α that is essential for mitosis
.
Science
.
2010
;
330
(
6011
):
1670
3
.
11.
Vigneron
S
,
Brioudes
E
,
Burgess
A
,
Labbé
JC
,
Lorca
T
,
Castro
A
.
Greatwall maintains mitosis through regulation of PP2A
.
EMBO J
.
2009
;
28
(
18
):
2786
93
.
12.
Peng
A
,
Yamamoto
TM
,
Goldberg
ML
,
Maller
JL
.
A novel role for greatwall kinase in recovery from DNA damage
.
Cell Cycle
.
2010
;
9
(
21
):
4364
9
.
13.
Álvarez-Fernández
M
,
Sánchez-Martínez
R
,
Sanz-Castillo
B
,
Gan
PP
,
Sanz-Flores
M
,
Trakala
M
, et al
.
Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals
.
Proc Natl Acad Sci USA
.
2013
;
110
(
43
):
17374
9
.
14.
Rogers
S
,
McCloy
RA
,
Parker
BL
,
Gallego-Ortega
D
,
Law
AMK
,
Chin
VT
, et al
.
MASTL overexpression promotes chromosome instability and metastasis in breast cancer
.
Oncogene
.
2018
;
37
(
33
):
4518
33
.
15.
Fatima
I
,
Barman
S
,
Uppada
J
,
Chauhan
S
,
Rauth
S
,
Rachagani
S
, et al
.
MASTL regulates EGFR signaling to impact pancreatic cancer progression
.
Oncogene
.
2021
;
40
(
38
):
5691
704
.
16.
Kang
Y
,
Massagué
J
.
Epithelial-mesenchymal transitions: twist in development and metastasis
.
Cell
.
2004
;
118
(
3
):
277
9
.
17.
Zidar
N
,
Boštjančič
E
,
Malgaj
M
,
Gale
N
,
Dovšak
T
,
Didanovič
V
.
The role of epithelial-mesenchymal transition in squamous cell carcinoma of the oral cavity
.
Virchows Arch
.
2018
;
472
(
2
):
237
45
.
18.
Stolfi
C
,
Marafini
I
,
De Simone
V
,
Pallone
F
,
Monteleone
G
.
The dual role of Smad7 in the control of cancer growth and metastasis
.
Int J Mol Sci
.
2013
;
14
(
12
):
23774
90
.
19.
Wei
W
,
Hu-Jie
C
.
Association of the infiltration of tumor-associated macrophages, expression of Smad7 protein and prognosis in oral squamous cell carcinoma
.
Arch Oral Biol
.
2018
;
95
:
22
9
.
20.
Zhuge
BZ
,
Du
BR
,
Meng
XL
,
Zhang
YQ
.
MASTL is a potential poor prognostic indicator in ER+ breast cancer
.
Eur Rev Med Pharmacol Sci
.
2017
;
21
(
10
):
2413
20
.
21.
Sun
XJ
,
Li
YL
,
Wang
LG
,
Liu
LQ
,
Ma
H
,
Hou
WH
, et al
.
Mastl overexpression is associated with epithelial to mesenchymal transition and predicts a poor clinical outcome in gastric cancer
.
Oncol Lett
.
2017
;
14
(
6
):
7283
7
.
22.
Marzec
K
,
Burgess
A
.
The oncogenic functions of MASTL kinase
.
Front Cell Dev Biol
.
2018
;
6
:
162
.
23.
Wang
L
,
Luong
VQ
,
Giannini
PJ
,
Peng
A
.
Mastl kinase, a promising therapeutic target, promotes cancer recurrence
.
Oncotarget
.
2014
;
5
(
22
):
11479
89
.
24.
Gouttia
OG
,
Zhao
J
,
Li
Y
,
Zwiener
MJ
,
Wang
L
,
Oakley
GG
, et al
.
The MASTL-ENSA-PP2A/B55 axis modulates cisplatin resistance in oral squamous cell carcinoma
.
Front Cell Dev Biol
.
2022
;
10
:
904719
.
25.
Lydiatt
WM
,
Patel
SG
,
Ridge
JA
,
O’Sullivan
B
,
Shah
JP
.
Staging head and neck cancers
. In:
AJCC cancer staging manual
. 8th ed.
AG Switzerland, IL, USA
:
Springer International Publishing
;
2017
. p.
55
181
.
26.
Wangmo
C
,
Charoen
N
,
Jantharapattana
K
,
Dechaphunkul
A
,
Thongsuksai
P
.
Epithelial-mesenchymal transition predicts survival in oral squamous cell carcinoma
.
Pathol Oncol Res
.
2020
;
26
(
3
):
1511
8
.
27.
Vera
J
,
Lartigue
L
,
Vigneron
S
,
Gadea
G
,
Gire
V
,
Del Rio
M
, et al
.
Greatwall promotes cell transformation by hyperactivating AKT in human malignancies
.
Elife
.
2015
;
4
:
e10115
.
28.
Álvarez-Fernández
M
,
Sanz-Flores
M
,
Sanz-Castillo
B
,
Salazar-Roa
M
,
Partida
D
,
Zapatero-Solana
E
, et al
.
Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer
.
Cell Death Differ
.
2018
;
25
(
5
):
828
40
.
29.
Chai
AWY
,
Lim
KP
,
Cheong
SC
.
Translational genomics and recent advances in oral squamous cell carcinoma
.
Semin Cancer Biol
.
2020
;
61
:
71
83
.
30.
Chow
LQM
.
Head and neck cancer
.
N Engl J Med
.
2020
;
382
(
1
):
60
72
.
31.
Colevas
AD
,
Yom
SS
,
Pfister
DG
,
Spencer
S
,
Adelstein
D
,
Adkins
D
, et al
.
NCCN guidelines insights: head and neck cancers, version 1.2018
.
J Natl Compr Canc Netw
.
2018
;
16
(
5
):
479
90
.
32.
D’Cruz
AK
,
Vaish
R
,
Dhar
H
.
Oral cancers: current status
.
Oral Oncol
.
2018
;
87
:
64
9
.
33.
Dasari
S
,
Tchounwou
PB
.
Cisplatin in cancer therapy: molecular mechanisms of action
.
Eur J Pharmacol
.
2014
;
740
:
364
78
.
34.
Nagel
R
,
Stigter-van Walsum
M
,
Buijze
M
,
van den Berg
J
,
van der Meulen
IH
,
Hodzic
J
, et al
.
Genome-wide siRNA screen identifies the radiosensitizing effect of downregulation of MASTL and FOXM1 in NSCLC
.
Mol Cancer Ther
.
2015
;
14
(
6
):
1434
44
.
35.
Katsuno
Y
,
Lamouille
S
,
Derynck
R
.
TGF-β signaling and epithelial-mesenchymal transition in cancer progression
.
Curr Opin Oncol
.
2013
;
25
(
1
):
76
84
.
36.
Ocasio
CA
,
Rajasekaran
MB
,
Walker
S
,
Le Grand
D
,
Spencer
J
,
Pearl
FM
, et al
.
A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct
.
Oncotarget
.
2016
;
7
(
44
):
71182
97
.
37.
Luo
L
,
Li
N
,
Lv
N
,
Huang
D
.
SMAD7: a timer of tumor progression targeting TGF-β signaling
.
Tumor Biol
.
2014
;
35
(
9
):
8379
85
.
38.
Wang
H
,
Nie
L
,
Wu
L
,
Liu
Q
,
Guo
X
.
NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21
.
Biochem Biophys Res Commun
.
2017
;
485
(
1
):
181
8
.
39.
Stolfi
C
,
De Simone
V
,
Colantoni
A
,
Franzè
E
,
Ribichini
E
,
Fantini
MC
, et al
.
A functional role for Smad7 in sustaining colon cancer cell growth and survival
.
Cell Death Dis
.
2014
;
5
(
2
):
e1073
.
40.
Boulay
J
,
Mild
G
,
Lowy
A
,
Reuter
J
,
Lagrange
M
,
Terracciano
L
, et al
.
SMAD7 is a prognostic marker in patients with colorectal cancer
.
Int J Cancer
.
2003
;
104
(
4
):
446
9
.
You do not currently have access to this content.